Epidermoid Carcinoma, Anus
Conditions
Keywords
anus, carcinoma, panitumumab, mitomycine, 5Fu, radiotherapy
Brief summary
Treatment is based on radiochemotherapy for locally advanced tumours. The objective of treatment is to provide a cure without resorting to abdominoperineal amputation, while preserving sphincter function. The prognosis is mainly related to tumour size and lymph node invasion. The large majority of patients do not show any spread remote from the tumour at the time of diagnosis (2). Recurrences are mainly of a local/regional nature and require abdominoperineal amputation. This type of intervention is not always possible or complete, which then gives rise to the particularly distressing risk of local progression, with survival at 3 years of approximately 30% (3). It is therefore very important to achieve a complete and permanent tumour response from initial treatment with radiochemotherapy. Furthermore, the use of an anti-EGFR antibody in combination with exclusive radiotherapy in ENT cancer was able to increase recurrence-free survival and overall survival in these patients. These data are in favour of the use of a combination of chemotherapy and anti-EGFR antibodies in epidermoid cancer of the anus.
Interventions
Radiotherapy : PTV1 45 Gy 5 weeks PTV2 20 Gy 2 weeks Chemotherapy : 5Fu (400 to 1000 mg/m²) mitomycin : 10 mg/m²
DRUGPanitumumab
3 or 6 mg/kg (according to dose level)
Sponsors
Federation Francophone de Cancerologie Digestive
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven epidermoid carcinoma of the anus * Locally advanced tumour without metastases * Stage T2\>3 cm or T3 or T4, irrespective of N * Stage N1-N3 irrespective of T stage (T1 to T4) * General condition WHO 0-1 * Life expectancy \> 3 months * Signed informed consent form * Age \> 18 years * Effective contraception in female and/or male patients having reached sexual maturity during treatment and up to 6 months after the end of treatment * CD4 \> 400 / mm3 * Measureable tumor on at least one of the following exams : MRI, endoscopic ultrasonography, clinical exam
Exclusion criteria
* Presence of metastases * Previous anti-EGFR therapy * Stage T1N0 or T2 \< 3 cm N0 * History of pelvic radiotherapy * At least one of the following laboratory test results: Neutrophils \< 1500 /mm3, platelets \< 100 000 /mm3, Hb \< 9 g/dl, leukocytes \< 3000/mm3, blood bilirubin \> 1.5 times the upper limit of the normal range, transaminase (ASAT and ALAT) \> 2.5 times the upper limit of the normal range, creatinine clearance \< 50 mL/min (Cockcroft's formula Appendix x), Mg2+ \< the lower limit of the normal range, Ca2+ \< the lower limit of the normal range * Significant coronary artery disease or myocardial infarction in the past year * Follow-up not possible due to psychological or geographic reasons * History of interstitial pneumonitis or pulmonary fibrosis * History of malignant disease in the past five years apart from basocellular skin carcinoma or in situ cervical carcinoma having received adequate treatment * Pregnant or breast-feeding women, women of child-bearing potential not having taken a pregnancy test.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Response to Treatment | 8 weeks evaluations after the end of the treatment by radiochemotherapy | Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance. The responses were validated by an independent committee: * In the event of a discrepancy between the investigator and the independent committee, the independent committee's response was used; * in case of uncertainty of the investigator on the response, the committee decided on the response in view of the clinical and morphological data; This endpoint was assessed 8 weeks after the end of treatment (week 15). A patient who died (regardless of cause) was considered a failure for the primary endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With Complete Response to Treatment | 16 weeks after the end of the treatement by radiotherapy | Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance according to the investigator's opinion |
| 3 Years Colostomy-free Survival (CFS) | At 3 years after inclusion | It was defined as the time from inclusion to the date of colostomy or death (from any cause). Patients alive without colostomy were censored at date of last news. If a patient had a shunt colostomy and continuity wasrestored, the patient was counted among the patients without a colostomy. |
| Recurrence-free Survival (RFS) at 3 Years | At 3 years after inclusion | It was defined as the time from inclusion to the date of first recurrence (local, regional, metastatic and second anal cancer) or death. Patients alive without recurrence were censored at date of last news. |
| Overall Survival (OS) at 12 Months | At 12 months after inclusion | The percentage was evaluated at 12 months using the Kaplan Meier estimation. In the safety part all the death collected during the study will be reported. |
Countries
France
Participant flow
Recruitment details
Between January 2016 and November 2017 (Phase II), 45 patients were enrolled by 15 french centers
Participants by arm
| Arm | Count |
|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy 5 FU = 400 mg days 1 to 4 weeks 1, 5 and 8 mitomicyne = 10 mg/m² day 1 week 1 and days 1, weeks 5 and 8 Panitumumab = 3 mg/kg days 1, weeks: 1, 3, 5, 8 and 10
radiochemotherapy: Radiotherapy : PTV1 45 Gy 5 weeks PTV2 20 Gy 2 weeks | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | 5Fu-mitomycine-panitumumab + Radiotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 31 Participants |
| Age, Continuous | 60.19 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 45 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment France | 45 participants |
| Sex: Female, Male Female | 36 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 45 |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 14 / 45 |
Outcome results
Primary
Percentage of Patients With Complete Response to Treatment
Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance. The responses were validated by an independent committee: * In the event of a discrepancy between the investigator and the independent committee, the independent committee's response was used; * in case of uncertainty of the investigator on the response, the committee decided on the response in view of the clinical and morphological data; This endpoint was assessed 8 weeks after the end of treatment (week 15). A patient who died (regardless of cause) was considered a failure for the primary endpoint
Time frame: 8 weeks evaluations after the end of the treatment by radiochemotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Partial response | 10 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Stability | 0 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Complete response | 30 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Progression | 4 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Death before the evaluation | 1 Participants |
Secondary
3 Years Colostomy-free Survival (CFS)
It was defined as the time from inclusion to the date of colostomy or death (from any cause). Patients alive without colostomy were censored at date of last news. If a patient had a shunt colostomy and continuity wasrestored, the patient was counted among the patients without a colostomy.
Time frame: At 3 years after inclusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy | 3 Years Colostomy-free Survival (CFS) | 68.8 % of patients Colostomy-free at 3 years |
Secondary
Overall Survival (OS) at 12 Months
The percentage was evaluated at 12 months using the Kaplan Meier estimation. In the safety part all the death collected during the study will be reported.
Time frame: At 12 months after inclusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy | Overall Survival (OS) at 12 Months | 95.6 % of patients alive at 12 months |
Secondary
Percentage of Patients With Complete Response to Treatment
Complete response was defined by the complete disappearance of the tumor on proctological examination and morphological examinations (MRI and/or echo-endoscopy) and the absence of secondary lesion appearance according to the investigator's opinion
Time frame: 16 weeks after the end of the treatement by radiotherapy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Complete response | 27 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Partial response | 9 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Stability | 1 Participants |
| 5Fu-mitomycine-panitumumab + Radiotherapy | Percentage of Patients With Complete Response to Treatment | Progression | 7 Participants |
Secondary
Recurrence-free Survival (RFS) at 3 Years
It was defined as the time from inclusion to the date of first recurrence (local, regional, metastatic and second anal cancer) or death. Patients alive without recurrence were censored at date of last news.
Time frame: At 3 years after inclusion
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5Fu-mitomycine-panitumumab + Radiotherapy | Recurrence-free Survival (RFS) at 3 Years | 62.2 % of pts with Reccurence-free at 3 yrs |